The present invention relates generally to implantable naturally derived biomaterials used to reinforce and/or regenerate native tissue.
Remodelable tissue grafts harvested as intact sheets from a mammalian source and processed to remove cellular debris advantageously retain the native structure of extracellular collagen matrix (ECM). This matrix of collagen fibers provides a scaffold to facilitate and support tissue ingrowth, particularly in bioactive graft materials, such as porcine small intestinal submucosa or SIS (Surgisis® Biodesign™, Cook Medical, Bloomington Ind.), that is processed to retain an effective level of growth factors and other constituents that stimulate angiogenesis.
While sheet-derived biomaterials advantageously retain the native structure of the collagen matrix, the use of individual sheets is not optimal for certain clinical applications, such as when repairing or reinforcing a body wall defect (e.g., a hernia). Single layer harvested sheets typically lack the requisite strength and durability when hydrated to permit fixation by suturing or other techniques and provide adequate reinforcement as the implanted collagen matrix degrades and is replaced. To address this limitation, overlapping sheets are laminated together by one of several known techniques, such as vacuum pressing, lyophlization (including press lyophilization), chemical cross-linking, etc., forming a more durable multilaminate construct comprising up to eight layers or more.
Multilaminate implantable ECM grafts have been demonstrated to be effective for clinical applications such as hernia repair, eliminating some of the complications associated with permanent polymeric surgical meshes, which are not resorbed by body. One potential issue with these multilaminate constructs is that the bonded layers can sometimes partially delaminate during handling after hydration, which can make the graft more difficult to suture into place. Furthermore, the separating layers of sheet material can provide pockets for the formation of a seroma, which can inhibit the remodeling process.
There remain needs for improved and/or alternative method of forming a multilaminate graft material. The present invention is addressed to those needs.
The present invention provides, in certain aspects an implantable surgical mesh comprising a plurality of sheets of a remodelable or bioactive collagenous material, such as a collagenous extracellular matrix that is harvested intact from a mammalian source (e.g., porcine small intestinal submucosa, bovine pericardium, porcine or human cadaveric dermis, etc.), wherein the one or more sheets of material are affixed to one another by thread, suture, or one or more strips of material, etc., interwoven through the adjoining sheets, thereby providing a primary or supplemental means of fixation to help prevent delamination of the graft or separation of the layers during handling and/or the initial period of remodeling.
In one aspect of the invention, the plurality of remodelable collagenous sheets is bonded together by a method such as vacuum pressing or lyobonding (bonding using the lyophlization process) prior to the interweaving member(s) being woven therethrough. In one embodiment, the interweaving members include one or more lines of bioresorbable suture material, thread, or another interweaving material that is woven through the graft in a lock stitch configuration or other suitable method. The pattern of stitching may vary according to clinical application and preference, one example including a series of suture lines forming diamond pattern or a single suture line, such as a spiral pattern. The stitching may extend across the entirety of the graft or be limited to the perhiperal regions to reinforce the edges. In an alternative embodiment, the layers of the graft may be secured with a series of discrete or unconnected stitches that are distributed across the graft, particularly along the periphery thereof.
Another aspect of the invention provides an interweaving member that comprises a length of bioresorbable suture, thread, yarn, or strips that include a bioactive agent, such as a medicaments (e.g., analgesics, anti-inflammatory agents, antibiotics, etc.) or agents/substances to stimulate or improve tissue remodeling (e.g., growth factors), whereby the agent is eluted from the interweaving member after implantation. The bioactive agent may be loaded into the suture material, applied or bonded to the outer surface, or incorporated into a separate drug-containing member comprises a separate portion of selected ones of the interweaving members.
A further embodiment of the invention provides a multilaminate graft comprising a first portion comprising one or more sheets of remodelable material, a second portion comprising one or more sheets of remodelable material, and a synthetic mesh material disposed therebetween. The first and second portions that form a ‘sandwich’ with the synthetic portion and are affixed to one another by at least one or more interweaving members and may be further bonded together by the same process used to form a multilaminate configuration (e.g., lyobonding, vacuum pressing, etc.) or by the use of a bonding agent (e.g., adhesive).
In certain embodiments, an inventive surgical graft will comprise a remodelable collagenous material and at least one interweaving member. In one such embodiment, the remodelable collagenous material will comprise a plurality of sheets disposed in a multilayer configuration, and the at least one interweaving member will be interwoven through the plurality of sheets of remodelable collagenous material such that the sheets are affixed together. In this and some other inventive constructs, at least one interweaving member present in the construct might comprise a bioresorbable material. Additionally or alternatively, an interweaving member might comprise a length of suture, thread, or yarn. An interweaving member might comprise a strip of material. An interweaving member might comprise a plurality of discreet suture points, e.g., woven through a plurality of sheets. An interweaving member, in certain aspects, will be interwoven through a plurality of sheets to create a series of stitches. These stitches might be spaced apart by an average distance greater than about 1.5 mm, with a preferred average distance of between 1-7 mm. Such stitches might comprise a plurality of lines forming a pattern across a surgical graft. A pattern might comprise intersecting lines of stitches, for example, such that the pattern comprises a diamond or other shaped configuration on a graft surface. In certain aspects, a pattern might comprise a line of stitches generally coextending with an adjacent line of stitches in at least one of a concentric or a parallel configuration. Additionally or alternatively, a surgical graft might include a first outer surface and a second outer surface facing opposite thereto, and this surgical graft might further comprise first and second regions of the first and second outer surface. In some forms, the stitch density in a first region of a graft will be greater than the stitch density in a second region, and this first region might generally extend along the periphery of a surgical graft. In other forms, the stitch density in a second region of a graft will be greater than the stitch density in a first region, and this second region might generally be disposed about the center of a surgical graft. Additionally or alternatively, a plurality of sheets might comprise a laminated configuration with at least one interweaving member being interwoven therethrough. Optionally, in some forms, a plurality of sheets will not be bonded to adjacent ones except by at least one interweaving member. An interweaving member might include at least one bioactive agent that is impregnated into and/or surface-applied to the interweaving members with the interweaving member being configured to deliver the bioactive agent into adjacent tissue when implanted. A bioactive agent might be selected from a group consisting of an analgesic, an anti-inflammatory agent, and an antibiotic. A bioactive agent might be effective for stimulation of tissue ingrowth into the plurality of sheets of remodelable collagenous material. In certain aspects, a remodelable collagenous material will comprise an extracellular matrix material that has been harvested intact from a mammalian source and subject to processing to render the material acellular while retaining a level of bioactivity therein. An interweaving member might comprise a durable material that is effective to provide reinforcement of a surgical graft during degradation of a remodelable collagenous material and the establishment of new host tissue to replace the remodelable collagenous material. A plurality of sheets might comprise a multilayer laminated configuration that includes a first group of laminated sheets, a second group of laminated sheets, and a synthetic mesh material disposed therebetween, for example, with the first and second group of laminated sheets being affixed to one another by at least one interweaving member. A synthetic mesh material might comprise polymeric strands having a diameter in the range of 0.04 mm to 1.0 mm, preferably in the range of 0.06 mm to 0.5 mm, and even more preferably less than 0.15 mm, with the strands being configured to persist and reinforce tissue about the site of implantation after remodeling of the remodelable extracellular matrix material is substantially complete.
In yet another embodiment, an inventive surgical graft comprises a remodelable extracellular matrix material and at least one interweaving member. The at least one interweaving member is selected from a group consisting of suture, thread and a strip of material. The remodelable extracellular matrix material comprises a plurality of sheets thereof disposed in a multilayer laminated configuration. The sheets are harvested intact from a mammalian source. The at least one interweaving member is interwoven through the plurality of sheets of remodelable extracellular matrix material to form a plurality of stitches further binding the plurality of laminated sheets together. The at least one interweaving member comprises a bioabsorbable material configured to undergo degradation after implantation of the surgical graft. In some forms, the graft will further comprise a bioactive agent that is impregnated into and/or surface-applied to the at least one interweaving member such that the bioactive agent is delivered into adjacent host tissue when implanted therein.
In another aspect, the invention provides a method for manufacturing a surgical graft. This method includes providing a plurality of sheets and at least one interweaving member. The at least interweaving member is selected from a group consisting of suture, thread and a strip of material. The plurality of sheets comprises a remodelable collagenous material that has been harvested from a mammalian source. The sheets are arranged in a multilayer configuration. The method further includes interweaving the at least one interweaving member through the plurality of sheets such that the plurality of sheets are affixed to one another. In some forms, this method will further comprise bonding the plurality of sheets together to form a laminated configuration. Additionally or alternatively, this method might further comprise adding a bioactive agent to the at least one interweaving member such that it is delivered from the at least one interweaving member into tissue disposed adjacent the surgical graft when implanted.
Other objects, embodiments, forms, features, advantages, aspects, and benefits of the present invention shall become apparent from the detailed description and drawings included herein.